Innovane 7.5 (Zopiclone Tablets BP 7.5 mg)

Indications

• Insomnia
• Sleep disorders

Dosage

Children: Zopiclone is not recommended for use in children and adolescents under 18 years of age.

Adults: The usual adult dose for insomnia is 7.5 mg taken immediately before bedtime. In some cases, a lower dose of 3.75 mg may be considered, particularly in elderly patients or those with hepatic impairment.

Mechanism of action

Zopiclone binds to the benzodiazepine receptor complex and modulates the GABA_BZ receptor chloride channel macromolecular complex. It acts as a full agonist at the benzodiazepine binding site on GABA_A receptors, particularly influencing the α1, α2, α3, and α5 subtypes, thereby enhancing the inhibitory effects of GABA, which results in therapeutic effects such as sedation and anxiolysis.

Pharmacodynamics

As a pyrazolopyrimidine derivative, Zopiclone exhibits hypnotic properties by selectively binding to the GABA_A receptor subunit, particularly the alpha-1 subtype. This selective action contributes to its sedative and anxiolytic effects. Its pharmacological profile is distinct from traditional benzodiazepines, despite its similar mechanism of action at the GABA_A receptor.

Pharmacokinetics

Zopiclone is rapidly absorbed after oral administration, with peak plasma concentrations occurring within approximately 1-2 hours. It undergoes hepatic metabolism primarily via cytochrome P450 enzymes, particularly CYP3A4, and has a relatively short half-life of about 5 hours. The drug is excreted mainly in the urine as metabolites, and caution is advised in patients with hepatic impairment due to altered clearance.

Contra-indications

• Myasthenia gravis
• Severe respiratory failure
• Sleep apnoea syndrome
• Acute alcohol intoxication
• Severe hepatic impairment

Adverse effects

• Abdominal pain
• Anterograde amnesia
• Anxiety
• Back pain
• Diarrhoea
• Dizziness
• Fatigue
• Hallucination
• Headache
• Increased risk of infection
• Nausea
• Sleep disorders
• Vomiting
• Confusion
• Diplopia
• Irritability
• Angioedema
• Abnormal behavior
• Depression
• Skin reactions
• Speech disorder
• Withdrawal syndrome

Interactions

• dronedarone+zopiclone: Moderate (increases exposure)
• cobicistat+zopiclone: Moderate (increases exposure)
• crizotinib+zopiclone: Moderate (increases exposure)
• idelalisib+zopiclone: Moderate (increases exposure)
• imatinib+zopiclone: Moderate (increases exposure)
• letermovir+zopiclone: Moderate (increases exposure)
• clarithromycin+zopiclone: Moderate (increases exposure)
• erythromycin+zopiclone: Moderate (increases exposure)
• mitotane+zopiclone: Moderate (decreases exposure)
• nilotinib+zopiclone: Moderate (increases exposure)

Precautions

• Use with caution in the elderly
• Use with caution in patients with hepatic impairment
• Use with caution in patients with renal impairment
• May cause prolonged sedation and affect the ability to drive or operate machinery
• Potential for abuse and dependence

Pregnancy

Avoid regular use during pregnancy due to risk of neonatal withdrawal symptoms; high doses during late pregnancy or labor may cause neonatal hypothermia, hypotonia, and respiratory depression.

Breast-feeding

Small amounts present in breast milk-avoid use while breastfeeding.

Storage

Store in a cool, dry place

Mechanism of action

Zopiclone exerts its action by binding on the benzodiazepine receptor complex and modulation of the GABA_BZ receptor chloride channel macromolecular complex. Both zopiclone and benzodiazepines act indiscriminately at the benzodiazepine binding site on α1, α2, α3 and α5 GABAA containing receptors as full agonists causing an enhancement of the inhibitory actions of GABA to produce the therapeutic (hypnotic and anxiolytic) and adverse effects of zopiclone.

Pharmacodynamics

Zopiclone is a nonbenzodiazepine hypnotic from the pyrazolopyrimidine class and is indicated for the short-term treatment of insomnia. While Zopiclone is a hypnotic agent with a chemical structure unrelated to benzodiazepines, barbiturates, or other drugs with known hypnotic properties, it interacts with the gamma-aminobutyric acid-benzodiazepine (GABA_BZ) receptor complex. Subunit modulation of the GABA_BZ receptor chloride channel macromolecular complex is hypothesized to be responsible for some of the pharmacological properties of benzodiazepines, which include sedative, anxiolytic, muscle relaxant, and anticonvulsive effects in animal models. Zopiclone binds selectively to the brain alpha subunit of the GABA A omega-1 receptor.